P1420: COMPARATIVE STUDY OF CYCLOSPORINE VERSUS TACROLIMUS IN ADDITION TO METHOTREXATE AS GRAFT VERSUS HOST DISEASE PROPHYLAXIS IN MATCHED SIBLING ALLOGENEIC STEM CELL TRANSPLANTATION OF SICKLE CELL DISEASE
Authors: Samar Alfaqawi, Mostafa Mohammed Saleh, Ahmed Kotb, Ghada Abdallah, Leena Ali, Reem Alasbali, Taimor Hussain, Haroon Alfadhil, Ahmed Bin Salman, Momen Nassani, Yazeed Baujaifer, Mohammed I. Sharif, Marwa Nassar, Sarah Samarkandi, Heba Madien, Amal Hejab, Ruah Alyamany, Ahmed Alnughmush, Abdullah Alamer, Ayman Saad, Mansour Alfayez, Abdelwahab Albabtain, Alfadel Alshaibani, Ahmad Alotaibi, Saud Alhayli, Marwan Shaheen, Syed O. Ahmed, Riad Elfakih, Amr Hanbali, Feras Alfraih, Walid Rasheed, Fahad Alsharif, Naeem Chaudhri, Hazza Alzahrani, Fahad Almohareb, Mahmoud Aljurf, Ali Alahmari
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Allogeneic stem cell transplantation (SCT) with HLA-identical sibling donor is the curative option for sickle cell disease (SCD) with excellent survival outcomes. Cyclosporine (CsA) or Tacrolimus (TAC) in combination with methotrexate (MTX) are the most commonly strategy used for graft versus host disease (GvHD) prophylaxis in this setting. Comparison of both agents in SCT of hematologic malignancies showed controversial conclusions by previous reports for efficacy and toxicities Aims: To compare efficacy and toxicities related to use of CsA versus TAC in addition to MTX as Graft versus host disease (GvHD) prophylaxis in SCD patients receiving matched sibling SCT. Methods: Patients aged ≥14 years old who underwent SCT for SCD between January 2011 and January 2022 at Adult Hematology, HSCT and cellular therapy section, Oncology center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia were initially reviewed. The standard GVHD prophylaxis was methotrexate with cyclosporine (MTX/CsA) in 63 patients and methotrexate with tacrolimus (MTX/TAC) in 33 patients. The conditioning regimen was FLU/ATG/BU14 for all patients recruited. Here, we report transplantation outcomes of both groups for acute GvHD (grade 3-4), chronic GvHD (extensive), veno-occlusive disease (VOD), CMV reactivation, transplant related mortality (TRM) and survival rates. GvHD and VOD diagnostic criteria were based on standard guidelines. We evaluated the renal toxicity to be defined as doubling of serum creatinine above baseline in the 1st 90 days post-transplant. Results: The whole cohort included 96 patients with median age was 21 (range: 14- 43), Males are 49 (51%) and females are 47 (49%).TAC group had higher median age 25 vs 20 years in CsA group; p=0.002. Median CD34 cell dose was higher in CsA group 5.4 × 106/kg. vs 4.4 × 106/kg; p= 0.045. Time for neutrophil recovery was longer 20 days in MTX/CsA vs 18 days in MTX/TAC; p= 0.007, with no difference for platelet recovery (21 v 21 days; p=0.7). We found no statistic significant difference between CsA group vs TAC group in acute GvHD and grade III to IV acute GvHD (20.6 vs 12.1%; p=0.3 and 7.9 vs 3%; p=0.5) respectively. Significant reduced chronic GvHD rate has been shown in TAC group 0% vs CsA group 25.4% p=0.002, with extensive chronic GvHD reported in 10 patients (15.9%), all in CsA arm. For other reported outcomes, no statistic significant differences were noted between the two groups for renal toxicity (32.3 vs 27.3%; p=0.6), VOD (1.6 vs 0%; p=0.5), CMV reactivation (73 vs 72.7%; p=0.5) and TRM (5.6 vs 2.9%; p=0.5). Mean follow up of the whole cohort was 122.9 months; with shorter median follow up in TAC group 20 months due to recent GvHD protocol switch to adapt TAC instead of CsA in our center. There was no significant difference for OS analysis between the two groups by Kaplan Meier analysis. Summary/Conclusion: TAC + MTX showed better effect in the prevention of chronic GvHD in SCD patients who received matched sibling SCT. No impact on other SCT outcomes and survival rates, however further prospective studies are warranted to assess the effect of TAC vs CsA combined with other novel suppressors for better and safe GvHD prophylaxis strategies. Keywords: Cyclosporin A, Sickle cell anemia, Allogeneic hematopoietic stem cell transplant, Tacrolimus